The toxic effects of exposure to PCP TCHQ and TCDD in splenocytes

  • 陳 綉敏

Student thesis: Doctoral Thesis

Abstract

Pentachlorophenol (PCP) was a commonly used fungicide herbicide insecticide and bactericide in industrial agricultural and domestic settings Technical grade PCP which was with contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) had immunosuppressive effects and that the immune system was the major target of PCDD/PCDFs toxicity Although the immune response after exposure to PCP or 2 3 7 8-tetrachlorodibenzo-p-dioxin (TCDD) has been studied the immunotoxic effects of exposure to both PCP and TCDD have not yet been reported Tetrachlorohydroquinone (TCHQ) is a major metabolite of PCP TCHQ has been identified as the main cause of PCP-induced genotoxicity due to reactive oxidant species (ROS) However the precise mechanisms associated with the immunotoxic effects of PCP and TCHQ remain unclear The aim of this study was to evaluate the effects on immune cells from mice intraperitoneally immunized with ovalbumin (OVA) and subsequently treated with PCP or TCDD alone or in combination by gavage (part I study) and to examine the effects of PCP and TCHQ on the induction of ROS and injury to primary mouse splenocytes (part II study) In part I study the animals were terminated on Day 7 and 14 and the spleen and plasma samples were collected for immunotoxicity evaluation The results indicate that the spleen/body weight ratio and splenocyte number was reduced by TCDD alone and this reduction was enhanced when TCDD was combined with PCP Exposure to TCDD alone or in conjunction with PCP suppressed many OVA-stimulated cytokines including IL-2 IFN-γ IL-4 IL-5 and IL-10 Furthermore the immunoglobulins IgG and IgM were suppressed in mice administered by PCP alone but the suppressive effects were greater in mice treated with TCDD alone or in combination with PCP Co-exposure to PCP and TCDD resulted in an antagonistic effect on TCDD-induced suppression of IFN-γ and IL-10 In part II study our results indicated that TCHQ was more toxic than PCP and that a high dose of TCHQ led to necrotic cell death of the splenocytes through induction of massive and sudden ROS and prolonged ROS-triggered ERK activation Inhibition of ROS production by N-acetyl-cysteine (NAC) partially restored the mitochondrial membrane potential inhibited ERK activity elevated caspase-3 activity and PARP cleavage and eventually switched the TCHQ-induced necrosis to apoptosis Thus this study demonstrates that PCP alone regardless of the presence of TCDD is immunotoxic and TCDD-induced IFN-γ suppression can be antagonized by PCP The results in this study also indicated that prolonged ERK activation is essential for TCHQ-induced necrosis and that ROS play a pivotal role in the different TCHQ-induced cell death mechanisms
Date of Award2014 Aug 8
LanguageEnglish
SupervisorYing-Jan Wang (Supervisor)

Cite this

The toxic effects of exposure to PCP TCHQ and TCDD in splenocytes
綉敏, 陳. (Author). 2014 Aug 8

Student thesis: Doctoral Thesis